Studies of carnitine biosynthesis and metabolism will continue, with the goals of further characterizing metabolic pathways related to carnitine biosynthesis and physiology of carnitine entry and exit from tissues, and determination of metabolic defects(s) in the carnitine deficiency syndromes. Feedback regulation of carnitine biosynthesis will be studied by feeding L-carnitine and the L-carnitine analogs D-carnitine and beta-chloro-gamma-trimethylaminobutyric acid to rats for specified periods. The capacity for carnitine biosynthesis in these animals will be tested by administering labeled precursors. Labeled and total carnitine will be determined in tissues, serum and urine. If either of these two analogs reduces carnitine biosynthesis and/or tissue carnitine levels, long-term feeding of these compounds will be started in an attempt to develop an animal model for the human carnitine deficiency syndromes. Carnitine fluxes in compartments of the human body will be studied by giving tracer doses of tritiated carnitine intravenously to volunteers and patients with carnitine deficiency. Disappearance of the tracer from the subjects' plasma will be monitored for 28 days. Using a three-compartment model (muscle, extracellular fluid, other tissues) we will determine carnitine flux into and out of these compartments. Finally, we will attempt to identify and characterize carnitine binding/ transport protein(s) in rat and human muscle membranes. If successful we will determine the presence and amount of these proteins in muscle of patients with carnitine deficiency.